与AZD5363、AZD8542、姜黄素或白藜芦醇联合治疗通过抑制PI3K/AKT和SHH信号通路诱导人胶质母细胞瘤细胞死亡。

Combined treatments with AZD5363, AZD8542, curcumin or resveratrol induce death of human glioblastoma cells by suppressing the PI3K/AKT and SHH signaling pathways.

作者信息

Mejía-Rodríguez Rosalinda, Romero-Trejo Daniel, González Rosa O, Segovia José

机构信息

Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Mexico.

Departamento de Matemáticas, Universidad Autónoma Metropolitana-Iztapalapa (UAM-I), Mexico.

出版信息

Biochem Biophys Rep. 2023 Jan 20;33:101430. doi: 10.1016/j.bbrep.2023.101430. eCollection 2023 Mar.

Glioblastoma (GBM) is a very aggressive tumor that presents vascularization, necrosis and is resistant to chemotherapy and radiotherapy. Current treatments are not effective eradicating GBM, thus, there is an urgent need to develop novel therapeutic strategies against GBM. AZD5363, AZD8542, curcumin and resveratrol, are widely studied for the treatment of cancer and in the present study we explored the effects of the administration of combined treatments with AZD5363, AZD8542, curcumin or resveratrol on human GBM cells. We found that the combined treatments with AZD5363+AZD8542+Curcumin and AZD8542+Curcumin+Resveratrol inhibit the PI3K/AKT and SHH survival pathways by decreasing the activity of AKT, the reduction of the expression of SMO, pP70S6k, pS6k, GLI1, p21 and p27, and the activation of caspase-3 as a marker of apoptosis. These results provide evidence that the combined treatments AZD5363+AZD8542+Curcumin and AZD8542+Curcumin+Resveratrol have the potential to be an interesting option against GBM.

胶质母细胞瘤（GBM）是一种极具侵袭性的肿瘤，具有血管生成、坏死的特点，并且对化疗和放疗具有抗性。目前的治疗方法无法有效根除GBM，因此，迫切需要开发针对GBM的新型治疗策略。AZD5363、AZD8542、姜黄素和白藜芦醇在癌症治疗方面得到了广泛研究，在本研究中，我们探究了联合使用AZD5363、AZD8542、姜黄素或白藜芦醇治疗对人GBM细胞的影响。我们发现，AZD5363+AZD8542+姜黄素以及AZD8542+姜黄素+白藜芦醇的联合治疗通过降低AKT活性、减少SMO、pP70S6k、pS6k、GLI1、p21和p27的表达以及激活作为凋亡标志物的caspase-3来抑制PI3K/AKT和SHH存活通路。这些结果证明，AZD5363+AZD8542+姜黄素以及AZD8542+姜黄素+白藜芦醇的联合治疗有可能成为治疗GBM的一个有吸引力的选择。